Osteoinducer Improves Osteogenic Efficacy of Calcium Phosphate Bone Substitute

Objectives: Calcium phosphate ceramics are frequently used as bone substitutes for bone tissue engineering due to its excellent osteoconductivity. However, they are not osteoinductive. A bone morphogenetic protein-2 (BMP2)-coprecipitated, layer-by-layer assembled biomimetic calcium phosphate particles (BMP2-cop.BioCaP) has been developed by our group as a potential osteoinducer. In this study, we combined this osteoinducer with a clinically applied bone substitute e.g. Straumann bone ceramic (SBC) to investigate if addition of BMP2-cop.BioCaP can enhance osteogenic efficacy of SBC
Methods: Seven groups were established (n=6): 1) SBC; 2) BioCaP; 3) BMP2-cop.BioCaP; 4) SBC mixed with BioCaP; 5) SBC mixed with BMP2-cop.BioCaP (Experimental group);6) SBC mixed with autogenous bone particles (Positive control); 7) Empty defect. These materials were implanted in rat cranial critical-sized bone defects (8mm diameter) for 4 and 12 weeks. Osteogenic efficacy and degradability of materials were evaluated using histological and histomorphometrical analysis. Data were statistically analyzed (ANOVA, Bonferroni, p<0.05)
Results: The volume density of newly formed bone in experimental group (0.56±0.08 mm³/mm³ ) was significantly higher than SBC (0.25±0.053 mm³/mm³) alone and was comparable with positive control(0.62±0.06 mm³/mm³) after 12 weeks. It indicates the addition of BMP2-cop.BioCaP into SBC improves osteogenic efficacy of SBC. Most newly formed bone was found along the border of bone defects; however, in the two groups with BMP2-cop.BioCaP, new bone was also formed in the center of bone defects. It explains the mechanism of BMP2-cop.BioCaP functioning as osteoinducer. BMP2-cop.BioCaP can improve osteogenic efficacy of SBC by stimulating independent new bone formation in the center of critical-sized bone defect. Moreover, after 12 weeks significantly lower amount of remaining SBC(0.14±0.01 mm³/mm³)was found in experimental group, indicating that osteoinducer also promoted degradation of SBC.
Conclusions: The combination of SBC and BMP2-cop.BioCaP can be a promising osteoinductive bone substitute for critical-sized bone defects.